Leptin is a hormone secreted by adipocytes which is thought to feed back to the hypothalamus and inhibit food intake as well as increase energy expenditure. The study was designed to test the hypothesis that macronutrient composition and a meal will both result in increases in serum leptin. Ten healthy subjects participated in this study, 5 obese and 5 lean. All subjects were weight stable and at maximum body weight. Subjects were instructed to follow a weight maintenance diet of either high carbohydrate or high fat for 5 days prior to the study. The subject was then given a meal which was consumed over 30 min. The composition of the meal was identical to the diet the subject had been following for the previous 5 days and the caloric content was 40% of daily caloric requirements for weight maintenance. Blood was drawn at various timepoints throughout the study and asssayed for leptin and other metabolic parametrs. The subjects were discharged and the process repeated with alternate diet after 4 weeks had passed. Overall, leptin levels were highly correlated with both BMR and percent body fat. At baseline, obese subjects had higher insulin, FFA, triglyceride and leptin levels. The acute meal resulted in increased insulin levels and decreased free fatty acids, however, no change in leptin was seen. By two way analysis of variance, macronutrient dietary composition did not affect leptin nor insulin levels, and only glycerol and FFA levels at 180 min post meal were affected by the diet. Conversely, only body habitus affected insulin and leptin levels. In conclusion, neither macronutrient dietary composition nor meal affect serum leptin in humans. Thus in humans, leptin may play a greater role in long term energy balance.